Source:http://linkedlifedata.com/resource/pubmed/id/21131601
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2011-1-18
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| pubmed:abstractText |
There are multiple mechanisms by which cells evade TGF-?-mediated growth inhibitory effects. In this report, we describe a novel mechanism by which cells become resistant to TGF-?-mediated growth suppression. Although having all the components of the TGF-? signaling pathway, different cell lines, RL, HaCaT, and BJAB, have different sensitivities toward TGF-?-induced growth suppression. The TGF-? resistance of RL, a B-cell lymphoma cell line, was due to ligand-induced downregulation of TGF-? receptor II (T?RII) and only transient TGF-? induced nuclear translocation of Smad2 and Smad3. With low-dose phorbol 12-myristate 13-acetate (PMA) or anti-IgM treatment, TGF-? sensitivity was restored by stabilizing T?RII expression and sustaining TGF-? signaling. The MEK inhibitor, U0126, blocked both PMA- and anti-IgM-induced upregulation of T?RII. In HaCaT and BJAB, two TGF-?-sensitive cell lines, which had higher basal levels of phospho-MEK and T?RII compared with RL, U0126 induced downregulation of T?RII and blocked subsequent TGF-? signaling. Similar results were also obtained with normal B cells, where MEK1 inhibitor downregulated T?RII and subsequent TGF-? signaling. Constitutively active MEK1, but not constitutively active ERK2, induced upregulation of T?RII. Furthermore, T?RII physically interacted with the constitutively active MEK1, but not with wild-type MEK1, indicating involvement of active MEK1 in stabilizing T?RII. Collectively, our data suggest a novel mechanism for MEK1 in regulating the sensitivity to TGF-? signaling by stabilizing T?RII.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Butadienes,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/MAP2K1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nitriles,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Transforming Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1,
http://linkedlifedata.com/resource/pubmed/chemical/U 0126,
http://linkedlifedata.com/resource/pubmed/chemical/phorbolol myristate acetate,
http://linkedlifedata.com/resource/pubmed/chemical/transforming growth factor-beta...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
1557-3125
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| pubmed:author | |
| pubmed:copyrightInfo |
©2010 AACR.
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| pubmed:issnType |
Electronic
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| pubmed:volume |
9
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
78-89
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| pubmed:meshHeading |
pubmed-meshheading:21131601-Blotting, Western,
pubmed-meshheading:21131601-Butadienes,
pubmed-meshheading:21131601-Cell Line,
pubmed-meshheading:21131601-Cell Line, Tumor,
pubmed-meshheading:21131601-Cell Proliferation,
pubmed-meshheading:21131601-Drug Resistance,
pubmed-meshheading:21131601-Enzyme Activation,
pubmed-meshheading:21131601-Enzyme Inhibitors,
pubmed-meshheading:21131601-HEK293 Cells,
pubmed-meshheading:21131601-Humans,
pubmed-meshheading:21131601-MAP Kinase Kinase 1,
pubmed-meshheading:21131601-Nitriles,
pubmed-meshheading:21131601-Protein Binding,
pubmed-meshheading:21131601-Protein-Serine-Threonine Kinases,
pubmed-meshheading:21131601-Receptors, Transforming Growth Factor beta,
pubmed-meshheading:21131601-Signal Transduction,
pubmed-meshheading:21131601-Tetradecanoylphorbol Acetate,
pubmed-meshheading:21131601-Transforming Growth Factor beta1
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| pubmed:year |
2011
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| pubmed:articleTitle |
Distinctive mechanism for sustained TGF-? signaling and growth inhibition: MEK1 activation-dependent stabilization of type II TGF-? receptors.
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| pubmed:affiliation |
Lymphocyte Cell Biology Section, Laboratory of Immunology, Biomedical Research Center, National Institute on Aging, National Institutes of Health, 251 Bayview Blvd., Baltimore, MD 21224, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Intramural
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